Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets

Bizymi, Nikoleta; Bjelica, Sunčica; Kittang, Astrid Olsnes; Mojsilović, Slavko; Velegraki, Maria; Pontikoglou, Charalampos; Roussel, Mikaël; Ersvær, Elisabeth; Santibáñez, Juan F.; Lipoldová, Marie; Papadaki, Helen Α.

doi:10.1097/hs9.0000000000000168

Cited by 46 publications

(50 citation statements)

References 101 publications

(297 reference statements)

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“…As summarized in Table 3 , a variety of immune cells contribute to the pathogenesis of hMDS, including cytotoxic T cells, regulatory T cells, natural killer cells, B-cells, monocytic cells, mesenchymal stem cells, and mastocytes [ 18 , 19 , 20 , 21 ]. Additional findings include the development of paroxysmal nocturnal hemoglobinuria (PNH) clones and the positivity of autoimmunity tests.…”

Section: Pathogenesismentioning

confidence: 99%

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Fattizzo

Serpenti

Barcellini

et al. 2021

Cancers

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Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring.

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Section: Pathogenesismentioning

confidence: 99%

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Fattizzo

Serpenti

Barcellini

et al. 2021

Cancers

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“…In humans, MDSCs have been related to worse outcomes in hematological malignancies (60,61); therefore, MDSCs were suspected to be involved in relapses after allo-HSCT. However, in the allo-HSCT setting, only a few prospective studies have reported a significantly higher probability of relapse in patients with higher M-MDSC frequencies than other patients, in the 30 days following allo-HSCT (52,53).…”

Section: Impact Of Mdscs On the Gvt Effectmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2020

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Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the recipient, after allo-HSCT) might mediate immune suppression through multiple mechanisms. However, it remains unclear how MDSCs can be distinguished from their normal myeloid counterparts in the hematopoietic stem cell donor graft and during immune reconstitution after allo-HSCT in the recipient. Our ability to understand their exact role in allo-HSCT is limited by the absence of a specific gene signature or surface markers for identifying MDSCs among myeloid cells and by their plasticity in different microenvironments. According to various studies, MDSCs might induce transplant tolerance and control graft vs. host disease (GVHD), but their impact on the graft vs. tumor effect (GVT) is not fully understood. In fact, we know that MDSCs commonly expand in patients with cancer, and they are thought to promote hematological malignancy progression. However, little is known about whether depleting them might be an effective strategy for enhancing GVT effects. Here, we review data published over the past 40 years on allo-HSCT to delineate the different MDSC subsets, and their abilities to induce transplant tolerance and preserve the GVT effect. This review will provide a basis for determining whether one MDSC subset might be proposed as the most appropriate candidate for cellular therapies, due to its ability to modulate GVHD.

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“…suppressing host immune responses [6][7][8]32 . The phenotypic marker of immature myeloid cells (CD33 + HLA-DR −/low ) is a characteristic feature of human suppressive MDSCs, which are further categorized into monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs) based on the differential expression of the CD14 and CD15 markers, respectively 33,34 . We have recently reported an expansion of M-MDSCs, which inhibited T cell functions via promoting regulatory T cell (Treg) differentiation during chronic viral infections [13][14][15][16] .…”

Section: Mdscs Expand During Chronic Hcv Infection Mdscs Play a Critmentioning

confidence: 99%

LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection

Thakuri¹,

Zhang²,

Zhao³

et al. 2020

Sci Rep

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HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that plays a pivotal role in regulating myeloid cell development via targeting HOXA1 gene expression. We and others have previously shown that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells, expand during chronic viral (HCV, HIV) infections. However, the role of HOTAIRM1 in the development and suppression of MDSCs during viral infection remains unknown. In this study, we demonstrate that the expressions of HOTAIRM1 and its target HOXA1 are substantially upregulated to promote the expressions of immunosuppressive molecules, including arginase 1, inducible nitric oxide synthase, signal transducer and activator of transcription 3, and reactive oxygen species, in CD33+ myeloid cells derived from hepatitis C virus (HCV)-infected patients. We show that HCV-associated exosomes (HCV-Exo) can modulate HOTAIRM1, HOXA1, and miR124 expressions to regulate MDSC development. Importantly, overexpression of HOTAIRM1 or HOXA1 in healthy CD33+ myeloid cells promoted the MDSC differentiation and suppressive functions; conversely, silencing of HOTAIRM1 or HOXA1 expression in MDSCs from HCV patients significantly reduced the MDSC frequency and their suppressive functions. In essence, these results indicate that the HOTAIRM1-HOXA1-miR124 axis enhances the differentiation and suppressive functions of MDSCs and may be a potential target for immunomodulation in conjunction with antiviral therapy during chronic viral infection.

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Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets

Cited by 46 publications

References 101 publications

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation

LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection

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